Strategies to Mitigate Breast-related Adverse Events in Patients with High-risk Biochemically Recurrent Prostate Cancer Receiving Enzalutamide Monotherapy: Perspectives and Challenges.

[BACKGROUND AND OBJECTIVE] Enzalutamide (Enza) is the only androgen receptor pathway inhibitor approved as monotherapy for high-risk biochemically recurrent prostate cancer. Breast-related adverse events (BRAEs) are common among patients treated with Enza monotherapy (Enza-Mono). We review relevant clinical trial data, including unpublished data, on measures to prevent BRAEs. Given the absence of data on mitigating strategies for Enza-associated BRAEs, we draw on pertinent prophylactic strategies used in studies of bicalutamide, a nonsteroidal antiandrogen with a similar mechanism of action. We critically discuss the clinical implications of such strategies to support decision-making in patients receiving Enza-Mono.

[METHODS] We searched PubMed for clinical trials on the safety of Enza-Mono, with a focus on BRAEs. We added relevant unpublished data from the EMBARK and ENACT trials. We also explored the literature and summarize prophylactic strategies for bicalutamide-induced BRAEs.

[KEY FINDINGS AND LIMITATIONS] In three trials involving 533 patients treated with Enza-Mono, Enza-Mono (160 mg/d) was commonly associated with gynecomastia (37-49%), breast pain or tenderness (14-26%), and/or nipple pain (15-30%). No prophylactic measures for BRAEs were protocol-specified in these studies. Previous studies with bicalutamide (150 mg/d) reported the benefits and relative tolerability of prophylactic radiation therapy and/or tamoxifen or prophylactic anastrozole to mitigate gynecomastia or breast pain.

[CONCLUSIONS AND CLINICAL IMPLICATIONS] Given the absence of data on prophylactic strategies for Enza-associated BRAEs, findings from bicalutamide studies could be extrapolated to Enza-Mono. Prospective trials are needed to optimize prophylactic strategies for BRAEs with Enza-Mono.